A potential model system for screening of methods purported to remove or disinfectant TSE agents is in initial stages of development in collaboration between LMD and the Laboratory of Analytical Chemistry, DMPQ, CBER, attempting to confirm reports that PC12 rat-pheochromocytoma cells infected with some strains of the scrapie agent undergo marked reduction in acetyl-cholinesterase neurotransmitter activity while maintaining normal levels of adrenergic activity. Should that pilot study succeed, PC12 cells might provide a suitable simplified assay to detect scrapie agent as a preliminary screening test of disinfectant and sterilization methods as described above. Methods that fail to remove infectivity of scrapie agent detectable in cell culture would clearly be inadequate for practical use~~where infecting doses of agent are potentially much higher than those detected by cell cultures-and would not merit further investigation in rodents. In FY 98, BSL-2 laboratory facilities and procedures suitable for the safe study of the infectious agents in cell cultures (using BSL-3 equipment and practices and elevated autoclave temperatures) were established, and basic cell-culture and HPLC-based enzymological methods needed for the model were successfully developed. This project will be continued in FY 99.